Revika Rachmaniar

260120130007

Quality Assurance

Program Pascasarjana
Magister Teknologi Farmasi dan Kosmetika
Fakultas Farmasi
Universitas Padjadjaran
Bandung
2013

Quality Assurance

A process, not an end-point

Must be independent of financial pressures
Must ensure that quality policies are followed
Must have final authority in product acceptance,
rejection and release to public
Integral to production, not an add-on
Responsible for day-to-day operations and for
longer term goal settings
Quantitative discipline with specified parameters

DEFINITIONS

QUALITY
The totality of features and characteristics of a

medicinal product and its ability to satisfy

stated and/or implied needs

QUALITY ASSURANCE
The sum total of the organized

arrangements made with the object of

ensuring that medicinal products are of the
quality required for their intended use.

DEFINITIONS

GOOD MANUFACTURING PRACTICE

(GMP)
That part of QA which ensures that products

are consistently produced and controlled to

the quality standards appropriate to their
intended use.

QUALITY CONTROL
That part of GMP which is concerned with

sampling, specifications and testing.

Quality relationships

QA
GMP

QC

Quality relationships
Quality Management
Quality Assurance
GMP

Quality Control

FACTORS IN DRUG QUALITY ASSURANCE

LEGISLATIVE
FRAMEWORK
-REGULATIONS

IMPORT
& EXPORT
CONTROL

HUMAN
RESOURCESPROFESSIONALS

RAW
MATERIALSACTIVE &
INACTIVE

MANUFACURING
PROCESSES
& PROCEDURES

PACKAGING

LABELLING &
PRODUCT
INFROMATION

DRUG
PRODUCT
QUALITY

STORAGE

QC &
ANALYSIS

TRANSPORT
DISTRIBUTION
DISPENSING
& USE
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Quality Assurance
Primary Functions
Quality Control
Analytical testing of products

Active and Non active material control

Sampling, inspecting and testing of incoming raw materials

Packaging and labeling components

Bottles, caps, foils, labels, measures, cartons

Physical inspection of product and operations at

critical intermediate stages
In-process controls, HHACCP

Control of product through its distribution

GSP, GDP ETC

Quality Must Be Designed Into A

Product

Quality is not an add-on: it begins with

research and development
Product quality criteria must be established
Detailed specifications provide quantitative
parameters for measurement
Written procedures document how quality is
attained and maintained
Continuous monitoring (sampling, testing) to
confirm quality is being built-into product
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Quality Assurance: Essential At

All Stages
Quality Assurance Cycle

Research
Development
Raw Materials
Facilities
Documentation
Equipment
Personnel

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Elements of the Quality Assurance

Cycle in Pharmaceutical
Manufacturing

Research
Development
Prototyping
Documentation
Raw Materials
Facilities
Equipment
Personnel and Supervision
Monitoring, Feedback, Follow-up
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Analytical Control Laboratory

Heart of Quality Management in
Pharmaceuticals

Academically trained and certified staff

Experienced supervision/management

Capable of performing complex analyses

Able to report honestly and in a timely manner

Equipment and instrumentation must be suitable for

performing testing

Access to reliable power, water and other stable

infrastructure
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Quality Control & Analysis

Qualification
Design, Installation, Process and Operational

Calibration
Daily and periodic

Validation
Equipment, Method and process

SOPs
Authorized, used and updated

Documentation
Systematic and well kept

Quality Manual
Quality manager, staff trained and motivated to comply.

Safety measures

13

Quality Assurance Throughout

the Manufacturing Process

Monitoring environmental conditions under

which products are manufactured/stored

Monitoring of air and water systems to prevent

contamination Air Handling Units

Monitoring of humidity

Monitoring of personnel

Feedback and follow-up

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Manufacturing Process and Procedures

Dispensing / Weighing
Mixing / Granulation / Preparation
Compression / Encapsulation / Filling
Equipment, Operational & Process
Qualification
Validation & calibration
Documentation and record keeping
Yield Reconciliation

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A Guiding Philosophy for Quality Assurance in

the Pharmaceutical Industry
Poor Quality Medicines:

Are a health hazard

Waste money for governments and consumers

May contain toxic substances that have unpredictable,

unintended consequences

Will not have a desired therapeutic effect

Does not save anyone any money in the long term

Hurt everyone patients, health care workers, policy

makers, regulators, manufacturers
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CONSEQUENCES OF QA BREACHES
Poor Treatment outcomes
High Health Bills
Treatment Failures & Deaths
Loss of Confidence in the Health
Services
Enormous Economic Losses
National Security Issue

17

What is GMP? (WHO)

Comprehensive system for ensuring

products are consistently produced and
controlled according to quality standards

Designed to minimize risks involved in any

pharmaceutical production that cannot be
eliminated through testing of final product
alone
Cross-contamination

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Major Risks in Pharmaceutical

Production

Contamination of products (microbial,

particulate or other)

Incorrect labels on containers

Insufficient active ingredient

Excess active ingredient

Poor quality raw materials
Poor formulation practices

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The Breadth of GMP

Covers all aspects of production including
Raw or starting materials
Finished products

Premises and environment

Equipment

personnel
Training
Hygiene
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GMP Principles

Must be built into manufacturing process

Prevents errors that cannot be eliminated

through quality control of finished product

Ensures all units of a medicine are of the same

(within specified parameters) quality

Poor medicines leads to loss of credibility for

everyone: manufacturers, health care workers
and governments

WHO Guidelines for GMP

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WHO Technical Guide to GMP

First prepared in 1967

Updated and revised regularly

Quality Management in the Drug Industry

outlines general concepts and principle
components of GMP

Good practices in production and quality

control describes implementation

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WHO Technical Guide to GMP

General Consideration
Licensed pharmaceutical products should be
manufactured only by licensed manufacturers
whose activities are regularly inspected by
competent national authorities

23

WHO Technical Guide to GMP

Key Concepts

Validation
Action of proving (in accordance with
principles of GMP) that any procedure,
process, equipment, material, activity, or
system actually leads to expected results

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WHO Technical Guide to GMP

Key Concepts

Qualification
Action of proving that any premises,
system, and items of equipment work
correctly and actually lead to expected
results

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Associated Concepts

Good Laboratory Practice (GLP)

Good Clinical Practice (GCP)
Clear language use
Effective record keeping
Design, installation, operational and
process qualification (DQ, IQ, OQ and PQ)
Self-inspection and self-regulation
Good Distribution Practice (GDP)

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Key Elements of GMP

(WHO Technical Guide)

Sanitation and hygiene

Qualification and validation

Complaints

Product recalls

Contract Production and Analysis

Self-Inspection and Quality Audits

27

Key Elements of GMP

(WHO Technical Guide)
Personnel
(Training, Hygiene)

Documentation

Premises
(Equipment)

Materials
(Supplies, Ingredients)

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Quality Assurance Before StartUp

Environmental and microbiologic control
and sanitation
To assure that finished dosage forms meet high
standards of quality and purity, an effective
sanitation program is required at all facilities
where such products are manufactured.
A successful extermination program must be
enforced within and outside the plant to control
insects and rodents.

29

Personal cleanliness and proper hair

covering and clothing should be required.
Floors, walls, and ceilings should be
resistant to external forces, capable of
being easily cleaned, and in good repair.
Adequate ventilation, proper temperature,
and proper humidity are other important
factors.

30

The water supply may be potable, distilled,

or deionized, and must be under adequate
pressure to keep the water flowing.
Deionization units should be monitored,
and the resins changed or regenerated
frequently.
to deliver water of consistently high
chemical and microbial quality as per
written compendia or in house
specifications.

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Quality assurance should review and

monitor the programs based on written
procedures that specify the details of
Sanitation, Cleaning, Ventilation and
Water.

32

Raw Materials
Quality assurance should check the original
containers of released raw materials for
cleanliness before they are taken to the
production department.
Most raw material, however, are weighed in an
environmental control weighing area, where
they are transferred to a secondary container
that circulates only inside the production
department.
This secondary container should be properly
labeled with a sticker that bears all the
information on the original container label.

33

Only released raw materials with proper

reassay date should be allowed to enter the
production department.
Raw material intended for used in specific
products should be stored together in an
area with proper identification (name, dosage
form, item number, lot number, weight, and
signatures).

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Manufacturing Equipment
Quality assurance personnel must ensure that
manufacturing equipment is designed, located,
and maintained so that it facilitates thorough
cleaning, is suitable for its intended use, and
minimizes potential for contamination during
manufacture.
Manufacturing equipment should be thoroughly
cleansed and maintained in accordance with
specific written directions.

35

Prior to the start of any production operation,

the quality assurance personnel should
ascertain that the proper equipment and
tooling for each manufacturing stage are
being used.
Equipment must be identified by labels
bearing the name, dosage form, item
number, and lot number of the product to be
processed.

36

Weighing and measuring equipment used in

production and quality assurance processes,
such as thermometer and balances, should
be calibrated and checked at suitable
intervals by appropriate methods.
Records of such tests should be maintained
by quality assurance and production
personnel.

37

Quality Assurance At
Start-Up
Raw Material processing
Only release, properly labeled raw materials are
allowed in the in-processing area.
Depending on the nature of the product, quality
assurance personnel should check and verify that
the temperature and humidity in there are within
the specified limits required for the product.
If the temperature and/or humidity is beyond the
specified limits, production must be informed and
corrective actions taken.

38

The specified in-process procedure is to be

checked, at each step in the process,
according to written in-process quality
assurance procedures.
Quality assurance personnel should verify
and document the
proper equipment
addition of ingredient
mixing time

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drying time
filtering
and mesh size of sieves used in screening.
At certain points, samples are to be taken to
the quality control laboratory for assay and
any other testing that is necessary to ensure
batch uniformity and purity.

40

Containers of in-process raw materials are

labeled with
product name
item number
lot number
and gross, tare, and net weights f the
contents.

41

Compounding
Quality assurance personnel are responsible
for ascertaining that all container of raw
materials are properly labeled and staged in
the compounding staging area, that they are
clean, and the manufacturing equipment is
properly identified as to product, strength,
item number, and lot number.

42

The production process begins with the set-up

of the manufacturing equipment to prepare the
finished dosage form within the specified limits
for the particular product.
At each significant step in the procedure,
quality assurance personnel verify that the
process is being performed in accordance with
the written directions and is conforming to
required standards.

43

A variable group of tests that are widely used

for in-process controls measure
characteristic including physical appearance,
color, odor, thickness, diameter, friability,
hardness, weight variation, disintegration
time, volume check, viscosity and pH.
Such in-process tests are designed to
ensure control of problems that can arise
during finished dosage form manufacturing.

44

Packaging Material Control

Packaging materials should not interact
physically or chemically with the finished
product to alter the strength, quality, or purity,
beyond specified requirement.
The compendium provides specifications and
test procedures for light resistance, wellclosed, tightly closed, and different types of
glass containers.

45

Good Manufacturing Practices require that

stability data be submitted for the finished
dosage form of the drug in the container
closure system in which it is to be marketed.

46

Labels Control
Production control issue s packaging form that
carries the name of the product, item number,
lot number, number of labels, inserts, and
packaging materials to be used, operations to
be performed, and the quantity to be packed.
A copy of this form is sent to the supervisor of
label control, who in turn counts out the required
number of labels.

47

If the lot number and expiration date of the

product are not going to be printed directly
on the line, the labels are run through a
printing machine, which imprints the lot
number and expiration date.
The labels are recounted and placed in a
separate container with proper identification
for future transfer to the packaging
department.

48

Quality assurance personnel inspects and

verifies all packaging components and
equipment to be used of the packaging
operation to ensure that
it has the proper identification
that the line has been thoroughly cleaned
that all material from the previous packaging
operation have been completely removed.

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FINISHED PRODUCT CONTROL

Final testing of finished product is made in

the quality control laboratories.
These tests are designed to determine
compliance with specifications.
Thus, the testing of the finished product for
compliance with predetermined standards
prior to release of the product for packaging
and subsequent distribution is a critical factor
for quality assurance.

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This testing, along with in-process testing,

assures that
each unit contains the amount of drug
claimed on the label,
all of the drug in each unit is available for
complete absorption,
the drug is stable in the formulation in its
specific final container closure system for its
expected shelf-life
the dosage units themselves contain no toxic
foreign substances.

51

Auditing
Good Manufacturing Practice requires that
the manufacturing process be adequately
documented throughout all stages of the
operation.
The history of each task, including the
starting materials, equipment used,
personnel involved in production and control
until completed packaging is complete,
should be recorded.

52

Before releasing the product for distribution,

quality assurance should evaluate the batch
records of all in-process tests and controls
and of all tests of the final product to
determine whether they conform to
specifications.

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